A double blind placebo controlled study to evaluate the effects of bexagliflozin on hemoglobin A1c in patients with type 2 diabetes and increased risk of cardiovascular adverse events

Phase 3

Completed

• Conditions: Type 2 diabetes and increased risk of cardiovascular adverse events; 10019280; 10018424; 10003216

• Registration Number: NL-OMON47856
• Lead Sponsor: Theracos Sub, LLC

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 23 April 2024

Recruitment & Eligibility

• Status: Completed
• Sex: Not specified
• Target Recruitment: 132

Inclusion Criteria

The study population will include:
1. Male or female adult subjects with an age *40 years
2. Subjects with a diagnosis of T2DM
3. Subjects with HbA1c values of 7.5 * 11%, inclusive
4. Subjects with fasting plasma glucose (FPG) * 250 mg/dL at screening
5. Subjects who have a regimen for treatment of T2DM that has been stable for
the past 3 months. A stable regimen is defined as: no changes in dose or
frequency of OHAs or GLP-1 agonists, or <20% variability in total daily insulin
dose
6. Subjects who present with at least one of the following 3 histories:
Group 1: A history of atherosclerotic vascular disease as defined by one or
more of the following:
a) myocardial infarction (MI) or ischemic (non-hemorrhagic) stroke > 3 months
but * 5 years prior to screening or
b) documented history of coronary, carotid, or peripheral arterial
revascularization (coronary artery bypass grafting must have occurred * 5 years
prior to screening)
Group 2: A history of NYHA class II or class III heart failure at the time of
screening with a left ventricular ejection fraction (LVEF) * 40% and no
subsequent LVEF > 40% documented within 6 months of screening. No more than 200
subjects with class II NYHA heart failure will be randomized in the study
Group 3: Age * 55 years with 2 or more of the following:
a) diabetes duration of * 10 years
b) uncontrolled hypertension defined as SBP > 140 mmHg despite 3 or more
anti-hypertensive medications
c) current smoking
d) urine albumin:creatinine ratio (UACR) > 30 mg/g
e) eGFR of 45 to 60 mL/min/1.73 m2, or
f) HDL < 1 mmol/L (38 mg/dL)
7. Female subjects of childbearing potential who are willing to use an adequate
method of contraception and to not become pregnant for the duration of the
study. Adequate contraceptive measures include, but are not limited to, oral
contraceptives, intrauterine devices, Depo-Provera, Norplant, hormonal
contraceptive implants, bilateral tubal ligation, partner with vasectomy,
condom or diaphragm plus contraceptive sponge, foam, or jelly, and abstinence
8. Subjects who are willing and able to return for all clinic visits and to
complete all study required procedures, including self-monitored blood glucose
(SMBG) measurement, and take run-in medication, missing no more than one dose
9. Subjects who receive anti-hypertensive medications at a stable dosage for *
2 weeks prior to randomization
10. Subjects who receive lipid modifying therapy on a stable regimen for 6
weeks prior to randomization
11. Subjects who have seated SBP < 170 mmHg and DBP < 110 mmHg at screening

Exclusion Criteria

Patients who exhibit any of the following characteristics will be excluded from
the study:
1. Diagnosis of type 1 diabetes mellitus or maturity*onset/diabetes of the
young (MODY)
2. Hemoglobinopathy that affects HbA1c measurement
3. Frequent symptomatic hypoglycemia (greater than one episode per week on
average)
4. Genitourinary tract infection within 6 weeks of screening or history of * 3
genitourinary infections requiring treatment within the last 6 months
5. Cancer, active or in remission for < 3 years (Non-melanoma skin cancer or
basal cell carcinoma or carcinoma in situ of the cervix will not be grounds for
exclusion)
6. History of alcohol or illicit drug abuse in the past 2 years
7. Evidence of abnormal liver function tests (total bilirubin or alkaline
phosphatase > 1.5 x upper limit of normal (ULN) with the exception of isolated
Gilbert*s syndrome); or alanine aminotransferase (ALT) or aspartate
aminotransferase (AST) > 2.5 x ULN
8. History of MI, stroke or hospitalization for heart failure in the prior 3
months
9. Evidence of NYHA class IV heart failure at screening or randomization
10. Presently scheduled for percutaneous coronary intervention, coronary artery
bypass grafting or any surgical procedure
11. Previous treatment with bexagliflozin or EGT0001474
12. Currently or within 3 months of taking any SGLT2 inhibitors
13. Any condition, disease, disorder, or clinically relevant laboratory
abnormality that, in the opinion of the PI, would jeopardize the subject*s
appropriate participation in this study or obscure the effects of treatment
14. Prior renal transplantation or evidence of nephrotic syndrome, defined as a
urine albumin: creatinine ratio (UACR) > 2000 mg/g, at screening
15. Implantation of a cardiac resynchronization therapy device within 3 months
prior to screening or intent to implant a cardiac resynchronization therapy
(CRT) within 6 months following screening
16. Diagnosis of peripartum or chemotherapy-induced cardiomyopathy within 12
months prior to screening
17. Symptomatic bradycardia or second or third degree atrioventricular block
without a pacemaker
18. eGFR, as calculated by the modification of diet in renal disease study
equation (MDRD), < 45 mL/min/1.73 m2 or requiring dialysis
19. Pregnant or nursing
20. Currently participating in another interventional trial

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary efficacy endpoint:<br /><br>* Change in HbA1c from baseline to week 24, compared to placebo</p><br>